The rs216009 single-nucleotide polymorphism of the CACNA1C gene is associated with phantom tooth pain.

Phantom tooth pain (PTP) is a rare and specific neuropathic pain that occurs after pulpectomy and tooth extraction, but its cause is not understood. We hypothesized that there is a genetic contribution to PTP. The present study focused on the CACNA1C gene, which encodes the α1C subunit of the Cav1.2 L-type Ca2+ channel (LTCC) that has been reported to be associated with neuropathic pain in previous studies. We investigated genetic polymorphisms that contribute to PTP. We statistically examined the association between genetic polymorphisms and PTP vulnerability in 33 patients with PTP and 118 patients without PTP but with pain or dysesthesia in the orofacial region. From within and around the CACNA1C gene, 155 polymorphisms were selected and analyzed for associations with clinical data. We found that the rs216009 single-nucleotide polymorphism (SNP) of the CACNA1C gene in the recessive model was significantly associated with the vulnerability to PTP. Homozygote carriers of the minor C allele of rs216009 had a higher rate of PTP. Nociceptive transmission in neuropathic pain has been reported to involve Ca2+ influx from LTCCs, and the rs216009 polymorphism may be involved in CACNA1C expression, which regulates intracellular Ca2+ levels, leading to the vulnerability to PTP. Furthermore, psychological factors may lead to the development of PTP by modulating the descending pain inhibitory system. Altogether, homozygous C-allele carriers of the rs216009 SNP were more likely to be vulnerable to PTP, possibly through the regulation of intracellular Ca2+ levels and affective pain systems, such as those that mediate fear memory recall.

Involvement of α- and ß-Adrenergic Receptors in Skeletal Muscle Blood Flow Changes During Hyper-/Hypocapnia in Anesthetized Rabbits.

OBJECTIVE: This study investigated the involvement of α1- and ß2-adrenergic receptors in skeletal muscle blood flow changes during variations in ETCO2. METHODS: Forty Japanese White rabbits anesthetized with isoflurane were randomly allocated to 1 of 5 groups: phentolamine, metaproterenol, phenylephrine, butoxamine, and atropine. Heart rate (HR), systolic blood pressure (SBP), common carotid artery blood flow (CCBF), masseter muscle tissue blood flow (MBF), and quadriceps muscle tissue blood flow (QBF) were recorded and analyzed at 3 periods: (1) baseline, (2) during hypercapnia (phentolamine and metaproterenol groups) or hypocapnia (phenylephrine, butoxamine, and atropine groups), and (3) during or after receiving vasoactive agents. RESULTS: MBF and QBF decreased during hypercapnia. The decrease in MBF was smaller than that in QBF. SBP and CCBF increased, while HR decreased. Both MBF and QBF recovered to their baseline levels after phentolamine administration. MBF became greater than its baseline level, while QBF did not fully recover after metaproterenol administration. MBF and QBF increased during hypocapnia. The increase rate in MBF was larger than that in QBF. HR, SBP, and CCBF did not change. Both MBF and QBF decreased to ∼90% to 95% of their baseline levels after phenylephrine or butoxamine administration. Atropine showed no effects on MBF and QBF. CONCLUSION: These results suggest the skeletal muscle blood flow changes observed during hypercapnia and hypocapnia may mainly involve α1-adrenergic but not ß2-adrenergic receptor activity.

A Case of Suspected Negative Pressure Pulmonary Edema after General Anesthesia.

Negative pressure pulmonary edema (NPPE) can occur rapidly after the release of an upper airway obstruction. In general anesthesia, NPPE can be caused by laryngospasm after extubation. This report describes a case in which NPPE was thought to have occurred after extubation during general anesthesia in a disabled person. The patient was a 28-yearold man, 160 cm in height and 56 kg in weight, who was scheduled for dental caries treatment under ambulatory general anesthesia due to intellectual disability. After induction of general anesthesia, nasal intubation was performed after sufficient oral suctioning to remove a large amount of serous secretion. After completion of dental treatment, pressurized extubation was performed after oral suctioning as sufficient spontaneous breathing and body movement were observed. Immediately after extubation, SpO2 dropped to 80%, subsequently recovering to 99% under oxygen administration at 5 liter/min with an oxygen mask. It dropped to approximately 85% again, however, when administration of oxygen was discontinued. Although communication with the patient was difficult, no expression of anguish or dyspnea was observed. A chest radiograph showed symmetric middle-lobe and lingular segment infiltrates, and the patient was transferred to the nearest general hospital. No obvious clinical findings other than a decrease in SpO2 were observed, suggesting NPPE as a result of airway narrowing due to secretions.

Prenatal asfotase alfa-mediated enzyme replacement therapy restores delayed calcification in a severe infantile form of hypophosphatasia model mice.

Hypophosphatasia (HPP) is a congenital disorder caused by mutations in the tissue-nonspecific alkaline phosphatase (TNALP) gene. The pathogenesis of HPP varies, ranging from severe cases in which there is total absence of fetal bone calcification, which leads to stillbirth, to relatively mild cases in which the effects are confined to the teeth, such as early loss of the primary teeth. In recent years, the establishment of enzyme supplementation as a treatment method has prolonged survival in patients; however, this approach does not provide sufficient improvement for failed calcification. Furthermore, the effects of enzyme replacement therapy on the jawbone and periodontal tissues have not yet been studied in detail. Therefore, in this study, we investigated the therapeutic effects of enzyme replacement therapy on jawbone hypocalcification in mice. Recombinant TNALP was administered to mothers before birth and newborns immediately after birth, and the effect of treatment was evaluated at 20 days of age. The treated HPP mice had improved mandible (mandibular length and bone quality) and tooth quality (root length of mandibular first molar, formation of cementum), as well as improved periodontal tissue structure (structure of periodontal ligament). Furthermore, prenatal treatment had an additional therapeutic effect on the degree of mandible and enamel calcification. These results suggest that enzyme replacement therapy is effective for the treatment of HPP, specifically in the maxillofacial region (including the teeth and mandible), and that early initiation of treatment may have additional beneficial therapeutic effects.

Usefulness of lateral cephalometric radiography for successful blind nasal intubation: a prospective study.

Background: This study aimed to investigate the relationship between pharyngeal morphology and the success or failure of blind nasotracheal intubation using standard lateral cephalometric radiography and to analyze the measurement items affecting the difficulty of blind nasotracheal intubation. Methods: Assuming a line perpendicular to the Frankfort horizontal (FH) plane, the reference point (O) was selected 1 cm above the posterior-most end of the hard palate. A line passing through the reference point and parallel to the FH plane is defined as the X-axis, and a line passing through the reference point and perpendicular to the X-axis is defined as the Y-axis. The shortest length between the tip of the uvula and posterior pharyngeal wall (AW), shortest length between the base of the tongue and posterior pharyngeal wall (BW), and width of the glottis (CW) were measured. The midpoints of the lines representing each width are defined as points A, B, and C, and the X and Y coordinates of each point are obtained (AX, BX, CX, AY, BY, and CY). For each measurement, a t-test was performed to compare the tracheal intubation success and failure groups. A binomial logistic regression analysis was performed using clinically relevant items. Results: The items significantly affecting the success rate of blind nasotracheal intubation included the difference in X coordinates at points A and C (Odds ratio, 0.714; P-value, 0.024) and the ∠ABC (Odds ratio, 1.178; P-value, 0.016). Conclusion: Using binomial logistic regression analysis, we observed statistically significant differences in AX-CX and ∠ABC between the success group and the failure group.

Effects of changes in end-tidal carbon dioxide tension on oral tissue blood flow and tissue oxygen tension during remifentanil infusion in rabbits.

PURPOSE: The aim of this study was to investigate the effects of end-tidal carbon dioxide tension (ETCO2) changes during remifentanil infusion on mandibular bone marrow tissue blood flow (BBF), masseter muscle tissue blood flow (MBF), mandibular bone marrow tissue oxygen tension (PbO2) and masseter muscle tissue oxygen tension (PmO2) in rabbits. METHODS: Ten male tracheotomized Japan White rabbits were anesthetized and ventilated with sevoflurane. ETCO2 was adjusted to 30 mmHg. After baseline measurement, CO2 was added to the inhaled air, and ETCO2 was increased to 40 and 60 mmHg. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), BBF, MBF, PbO2, and PmO2 were recorded with and without remifentanil infusion at 0.4 µg/kg/min. RESULTS: Two-way repeated measures analysis of variance showed no interaction between ETCO2 and remifentanil in all variables. Remifentanil infusion produced decreases in HR, SBP, MAP, BBF and MBF compared with those without remifentanil infusion, while it did not affect DBP, PbO2 and PmO2. Elevation of ETCO2 from 30 to 60 mmHg produced decreases in HR and MBF, and increases in SBP, DBP, MAP and BBF, while it did not affect PbO2 and PmO2. CONCLUSION: PbO2 and PmO2 remained unchanged despite changes in BBF and MBF during ETCO2 change with or without remifentanil infusion.

Airway Management Strategy Using Seldinger Minitracheostomy Kit to Prevent Airway Obstruction after Oral Cancer Surgery: A Retrospective Study.

A minitracheostomy (MTS) is performed after surgery for oral cancer at our institution in patients who are at risk of postoperative airway obstruction. The aim of this study was to evaluate outcomes of preventive airway management with this procedure. A total of 105 patients undergoing preventive airway management with a Seldinger MTS kit after oral cancer surgery between October 2014 and March 2020 were enrolled. Information on patient characteristics, time required for the MTS, duration of tracheal cannula placement, and MTS-related complications was obtained from both the medical and anesthesia records. In addition, the numbers of postoperative instances of tracheotomy between April 2009 and September 2014 and extubation between October 2014 and March 2020 were also counted for a comparison. The time required for an MTS was 3.2±2.6 min. Minor complications, including mild subcutaneous or mediastinal emphysema and bleeding, were found in 5 patients, but all recovered in a short time. The median duration of tracheal cannula placement was 2 days, with a range of from 0 to 8 days. A total of 348 oral cancer surgeries were performed between April 2009 and September 2014. Among patients undergoing these procedures, 111 underwent a tracheostomy (32%), 235 extubation (68%), and 2 sustained intubation. A total of 580 oral cancer surgeries were performed between October 2014 and March 2020. Here, 121 patients underwent a tracheostomy (21%), 105 an MTS (18%), and 354 extubation (61%). The results suggest that an MTS can be performed safely and smoothly with no significant complications. They also suggest that an MTS reduces the need for a full tracheostomy and the risk of airway obstruction after extubation. We conclude that airway management strategy with an MTS is a useful option in preventing airway obstruction following oral cancer surgery.

Effects of intrathecal opioids on cesarean section: a systematic review and Bayesian network meta-analysis of randomized controlled trials.

PURPOSE: We aimed to compare the beneficial and harmful effects of opioids used as adjuncts to local anesthetics in patients undergoing cesarean section under spinal anesthesia. METHODS: We searched electronic databases and ClinicalTrials.gov from their inception until March, 2021 without language restrictions. The primary outcome was the complete analgesia duration (Time to VAS > 0). Data were synthesized using the Bayesian random-effects model. Evidence confidence was evaluated using the Confidence In Network Meta-Analysis. RESULTS: We identified 66 placebo-controlled randomized controlled trials (RCTs) comprising 4400 patients undergoing elective cesarean section. Compared with the placebo, intrathecal opioids (fentanyl, sufentanil, and morphine) significantly prolonged the analgesia duration by 96, 96, and 190 min, respectively (mean difference). Despite morphine ranking first, opioid efficacy was similar; the results were inconsistent with respect to other analgesic outcomes. Except for diamorphine, all opioids were associated with significant increases in the pruritus incidence. Sufentanil and morphine were associated with increases in the respiratory depression incidence. CONCLUSIONS: We confirmed that intrathecal opioids benefit postoperative analgesia. Although morphine seems to be the most appropriate agent, some results were inconsistent, and the evidence confidence was often moderate or low, especially for adverse outcomes. Well-designed RCTs with an evidence-based approach are imperative for determining the most appropriate opioid for cesarean sections.

Remifentanil infusion during desflurane anesthesia reduces tissue blood flow while maintaining blood pressure and tissue oxygen tension in the masseter muscle and mandibular bone marrow.

The aim of this study was to compare changes in tissue blood flow and tissue oxygen tension in the masseter muscle and mandibular bone marrow induced by remifentanil under desflurane or sevoflurane anesthesia. Eleven male tracheotomized Japan White rabbits were anesthetized with desflurane or sevoflurane under mechanical ventilation. The order of the inhalation of desflurane or sevoflurane was randomized. Desflurane or sevoflurane was administered at 1.0 minimum alveolar concentration and remifentanil was infused at 0.4 µg/kg/min. Observed variables included heart rate (HR), blood pressure (BP), common carotid artery blood flow (CCBF), mandibular bone marrow tissue blood flow (BBF), masseter muscle tissue blood flow (MBF), mandibular bone marrow tissue oxygen tension (PbO2), and masseter muscle tissue oxygen tension (PmO2). Two way repeated measures ANOVA showed no interaction between volatile anesthetics and remifentanil infusion except for MBF. There were significant differences in HR, SBP, DBP, MAP and CCBF between desflurane and sevoflurane groups. There were also significant differences in HR, SBP, DBP, MAP, CCBF, BBF and PbO2 before, during and after remifentanil infusion. Desflurane reduced tissue blood flow in the masseter muscle and mandibular bone marrow while better maintained HR and BP than sevoflurane. Under remifentanil infusion, although both anesthetics reduced tissue blood flow, tissue oxygen tension was maintained in masseter muscle and mandibular bone marrow.

New Device for Securing Nasotracheal Intubation Tube During Oral and Maxillofacial Surgery.

Since 2018, we have been using a 3D printer to fabricate a proprietary device for fixing nasotracheal tubes. The aim of this retrospective study was to investigate the impact of this nasotracheal intubation (NTI) fixation device. It has been used in 335 patients undergoing general anesthesia for oral and maxillofacial surgeries. No necrosis or permanent tissue damage was observed, and none of the patients developed complications requiring treatment. No unintentional tube-related incidents such as extubation, dislocation of the tube, or disconnection between the tube and the artificial respiration circuit occurred either. This fixation device offers three advantages: safety, no impediment to surgery, and minimal invasiveness. Of these, safety is the most important. The high degree of immobilization it offers makes it possible to prevent injury to the nasal ala when the tracheal tube is tugged to the cranial side. There is also a high degree of immobilization at the connection site between the tracheal tube and anesthesia circuit, making it possible to prevent disconnection due to intraoperative pressure. In addition, safety during fixation is less likely to differ depending on the degree of proficiency of the individual anesthesiologist. The presence of a groove through which the sampling tube of the capnometer can be passed makes it possible to prevent the problem of flexion of the sampling tube, rendering detection impossible during surgery. Thus, use of this fixation device offers the potential to improve immobilization of the tracheal tube and increase intraoperative safety. However, there remain several problems that need to be addressed with this novel device. Further improvements aimed at enhancing safety are planned, therefore.

Effects of Stellate Ganglion Blockade on Muscle Blood Flow During Hypercapnia.

This study investigated the effects of a unilateral stellate ganglion block (SGB) on ipsilateral and contralateral masseter muscle blood flow during permissive hypercapnia. Eight male Japanese white rabbits were anesthetized with isoflurane. Observed variables included heart rate (HR), blood pressure (BP), left common carotid artery blood flow (LCBF), left and right masseter muscle tissue blood flow (LMBF and RMBF), and left femoral quadriceps muscle tissue blood flow (LQBF). Variable measurements were taken at a baseline end-tidal carbon dioxide tension (EtCO2) of 40 mm Hg and repeated at an elevated EtCO2 of 60 mm Hg prior to and after administration of a left SGB. HR decreased, while systolic BP was elevated during hypercapnia and after the SGB. LCBF increased during hypercapnia and after the SGB. LMBF and RMBF decreased to 75% and LQBF decreased to 60% of their respective baseline values during hypercapnia. After the SGB, LMBF was restored, reapproximating its baseline, but RMBF and LQBF further decreased to 55 and 45% of their respective baseline values. In conclusion, unilateral SGB restored the ipsilateral masseter muscle blood flow that had been reduced during hypercapnia. In contrast, the SGB exacerbated the hypercapnia-induced reduction in blood flows in the contralateral masseter muscle and the femoral quadriceps muscle.

Recurrent aspiration pneumonia due to bilateral associated laryngeal paralysis after tooth extraction under general anesthesia: a case report.

BACKGROUND: Associated laryngeal paralysis is a clinical condition merged with other cranial nerve disorders associated with vocal cord paralysis. It is a rare complication in patients after general anesthesia. Here, we report our experience with a patient who developed associated laryngeal paralysis after oral surgery. CASE PRESENTATION: A healthy 31-year-old man underwent extraction of horizontally impacted wisdom teeth in the bilateral mandible under general anesthesia. During the surgery, no significant changes in respiratory and cardiovascular parameters or neurosurgical abnormalities occurred. After the surgery, the patient was diagnosed with aspiration pneumonia. Furthermore, the results of otorhinolaryngological and neurological examinations led to a diagnosis of a combination of bilateral glossopharyngeal and vagus nerve paralysis, right recurrent nerve paralysis, and right hypoglossal nerve paralysis. In this case, seriously associated peripheral laryngeal paralysis with repeated episodes of aspiration pneumonia improved in approximately 6 months with rehabilitation and vitamin B12 administration, and no complications remained. CONCLUSIONS: We suggest that the anesthesiologist should take care of each procedure minutely. It is important to diagnose cases of nerve palsy as soon as possible to reduce the damage. Having had experience with this case, we believe sharing our experience with anesthesiologists is important.

[Prevention of Postoperative Delirium and Agitation in a Patient with Anti-NMDA Receptor Encephalitis: A Case Report].

A 41-year-old woman with anti-N-methyl-D-aspartate (NMDA) receptor encephalitis, characterized by vari- ous psychiatric disturbances, was scheduled for laparo- scopic salpingo-oophorectomy. Anesthesia was induced with fentanyl, propofol and rocuronium, and maintained with intravenous propofol combined with epidural anesthesia (T10-11). The patient received 20 mEq of MgSO4 after induction. MgSO4 administrations were repeated at the end of surgery and every 12 hours for 48 hours after the operation. The operation was per- formed successfully, without any troubles. Trachea was extubated in the operating room. The cognitive dys- function was not observed postoperatively. There was no complication and no unexpected event postopera- tively. One month after surgery, the patient's clinical symptom began to improve. The resection of tumor is recommended as a thera- peutic treatment ; however, there has been few report of the management of postoperative cognitive dysfunc- tion for patients with NMDA receptor antibodies. These patients were more likely to experience a post- operative cognitive dysfunction associated with a poor outcome. We, therefore, administered magnesium sul- fate, NMDA antagonist to prevent postoperative delir- ium. In the present case, magnesium sulfate might have prevented the incidence of postoperative delirium without any complications. The prophylactic magne- sium administration could prevent postoperative delir- ium and agitation safely.

Dose-dependent remifentanil decreases oral tissue blood flow during sevoflurane and propofol anesthesia in rabbits.

PURPOSE: The aim of this study was to investigate the effect of remifentanil continuous infusion on the blood flow in rabbit oral tissue during propofol and sevoflurane anesthesia, as well as its dose dependency. MATERIALS AND METHODS: Sixteen male tracheotomized Japan white rabbits were anesthetized with propofol or sevoflurane under mechanical ventilation. The infusion rate of remifentanil was 0.1, 0.2, 0.4, 0.8, and 1.6 µg·kg(-1)·min(-1), respectively, for 20 minutes. Observed variables were systolic blood pressure (SBP), diastolic blood pressure, mean arterial pressure (MAP), heart rate (HR), common carotid artery blood flow, tongue mucosal blood flow (TBF), mandibular bone marrow blood flow (BBF), masseter muscle blood flow (MBF), upper alveolar tissue blood flow (UBF), and lower alveolar tissue blood flow (LBF). RESULTS: HR, SBP, MAP, TBF, BBF, MBF, UBF, and LBF showed dose-dependent decreases during remifentanil infusion with both propofol and sevoflurane anesthesia. The decreases in BBF, MBF, UBF, and LBF explained as a percent change were greater than those in HR, SBP, MAP, and TBF. In the sevoflurane group, there were no changes in diastolic blood pressure and common carotid artery blood flow during remifentanil infusion. CONCLUSION: Our findings suggest that infusion of remifentanil reduces TBF, BBF, MBF, UBF, and LBF in a dose-dependent manner without a significant reduction in MAP during propofol and sevoflurane anesthesia.